Pain and depression are two of the most prevalent and treatable cancer-related symptoms, each present in at least 20-30% of oncology patients. Both symptoms, however, frequently go either unrecognized and/or under-treated. Four common harriers include underdetection, inadequate initial treatment, failure to monitor adherence and symptom response, and failure to adjust treatment in patients not responding or intolerant of initial therapy. Nurse-delivered care management models proven effective for depression in primary care have considerable potential for optimizing both depression and pain care in cancer patients. Therefore, we propose to conduct the Indiana Cancer Pain and Depression (INCPAD) study, a randomized clinical trial conducted in a statewide network of community-based cancer clinics located in both rural and urban oncology practices. INCPAD will enroll 480 patients with cancer-related pain (n = 240) or clinical depression (n = 240), randomizing them to either the intervention or usual care control group. The intervention will be based upon the empirically-validated Three-Component Model (TCM) which for INCPAD will involve collaboration between the oncology practice, a centralized nurse care manager, and a supervising pain-psychiatrist. In this trial, TCM will involve an innovative telemedicine approach involving automated home-based symptom monitoring coupled with telephone-based nurse care management. All subjects will undergo comprehensive outcome assessment at baseline, 1, 3, 6 and 12 months by interviewers blinded to treatment group. Our principal aim is to test whether TCM is more effective than usual care in improving the co-primary outcomes of depression and pain. Secondarily, we will test the intervention's impact on health-related quality of life, cost-effectiveness of care, and treatment satisfaction. This intervention has the potential for improving symptom management in cancer patients across a wide range of oncology practices that may be geographically dispersed and varying in location (rural or urban), health plan, payer, or other characteristics. Furthermore, if proven effective for depression and pain, TCM could readily be expanded to reducing barriers and improving care of other cancer-related symptoms.